Rejuvenating Effector/Exhausted CAR T Cells to Stem Cell Memory-Like CAR T Cells By Resting Them in the Presence of CXCL12 and the NOTCH Ligand.

ABSTRACT: T cells with a stem cell memory (T_SCM) phenotype provide long-term and potent antitumor effects for T-cell transfer therapies. Although various methods for the induction of T_SCM-like cells in vitro have been reported, few methods generate T_SCM-like cells from effector/exhausted T cells. We have reported that coculture with the Notch ligand-expressing OP9 stromal cells induces T_SCM-like (iT_SCM) cells. Here, we established a feeder-free culture system to improve iT_SCM cell generation from expanded chimeric antigen receptor (CAR)-expressing T cells; culturing CAR T cells in the presence of IL7, CXCL12, IGF-I, and the Notch ligand, hDLL1. Feeder-free CAR-iT_SCM cells showed the expression of cell surface markers

SUBMITTER: Ando M 

PROVIDER: S-EPMC9973402 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature